Featured Research

from universities, journals, and other organizations

Enzyme Involved In Cocaine Addiction Identified By Scientists At Yale And Rockefeller Universities

Date:
March 29, 2001
Source:
Yale University
Summary:
Researchers at Yale and Rockefeller Universities have found that an enzyme called Cdk5 regulates the action of dopamine, a chemical messenger associated with cocaine's "rush" and with addiction to cocaine and other drugs.

New Haven, Conn. -- Researchers at Yale and Rockefeller Universities have found that an enzyme called Cdk5 regulates the action of dopamine, a chemical messenger associated with cocaine's "rush" and with addiction to cocaine and other drugs.

According to Jingshan Chen, assistant professor of psychiatry at Yale, the Cdk5-related process leads to changes in brain cells that are thought to play a key role in cocaine addiction.

"This work adds to our increasing understanding of the changes that cocaine causes in the brain at the molecular level to produce addiction," said Eric Nestler, who worked on the study while he was professor of pharmacology and neurobiology at Yale. "With this knowledge it should be possible to eventually develop more effective treatments for cocaine addiction."

The research, published in today's issue of Nature, focuses on long-term neuroadaptive changes associated with drug addiction. One of these long-term changes first identified by Jane Taylor at Yale, is the induction of stable delta-FosB proteins in nucleus accumbens, a brain region that mediates the drug's rewarding and reinforcing effects. Delta-FosB is a transcription factor, which means that it regulates expression of other genes.

Using a new technology called DNA array analysis, the team found that exposure to cocaine caused increased levels of delta-FosB in dopamine-sensitive brain cells. The delta-FosB then triggered an increase in Cdk5 levels. Genetically engineered transgenic mice or rats injected with cocaine for eight days showed elevated levels of Cdk5 compared with control animals. Nestler said the cocaine-exposed rats also showed increases in motor activity after they were given cocaine. Rats that were treated with roscovitine, a drug that slows the action of Cdk5, displayed motor activity that was nearly double that of untreated rats.

"Since Cdk5 plays an important role in re-organization of cellular structures of neurons, we think that delta-FosB may mediate some long-term structural changes via Cdk5 and lead to drug addiction," said Chen.

Nestler said that chronic cocaine use normally causes sensitization, which progressively increases the degree of locomotor activity. When he and the team infused a Cdk5 inhibitor into the nucleus, cocaine's ability to produce sensitization was markedly enhanced. Therefore, the increase in Cdk5 induced by delta-FosB seems to represent a normal brake on the effects of cocaine.

"These findings indicate that cocaine-induced increases in Cdk5 levels may dull the brain's response to cocaine exposure," said Nestler, who is now Chair of the Department of Psychiatry at the University of Texas Southwestern Medical Center at Dallas. "This could contribute to a phenomenon observed in human addicts, who often report a diminishing pleasurable effect of cocaine with repeated use."

In addition to Chen and Nestler, other researchers on the study included Jane Taylor of Yale, James Bibb, Paul Greengard, Per Svenningsson, Akinori Nishi, Gretchen Snyder, Zachary Sagawa and Angus Nairn of the Rockefeller University; and Charles Ouimet from Florida State University.


Story Source:

The above story is based on materials provided by Yale University. Note: Materials may be edited for content and length.


Cite This Page:

Yale University. "Enzyme Involved In Cocaine Addiction Identified By Scientists At Yale And Rockefeller Universities." ScienceDaily. ScienceDaily, 29 March 2001. <www.sciencedaily.com/releases/2001/03/010328075033.htm>.
Yale University. (2001, March 29). Enzyme Involved In Cocaine Addiction Identified By Scientists At Yale And Rockefeller Universities. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2001/03/010328075033.htm
Yale University. "Enzyme Involved In Cocaine Addiction Identified By Scientists At Yale And Rockefeller Universities." ScienceDaily. www.sciencedaily.com/releases/2001/03/010328075033.htm (accessed July 24, 2014).

Share This




More Mind & Brain News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
China's Ageing Millions Look Forward to Bleak Future

China's Ageing Millions Look Forward to Bleak Future

AFP (July 24, 2014) China's elderly population is expanding so quickly that children struggle to look after them, pushing them to do something unexpected in Chinese society- move their parents into a nursing home. Duration: 02:07 Video provided by AFP
Powered by NewsLook.com
Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. Video provided by Newsy
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins